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Gene Review

SIS2  -  phosphopantothenoylcysteine decarboxylase...

Saccharomyces cerevisiae S288c

Synonyms: HAL3, Halotolerance protein HAL3, Phosphopantothenoylcysteine decarboxylase subunit SIS2, Sit4 suppressor 2, YKR072C
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High impact information on SIS2

  • The yeast Ppz protein phosphatases and the Hal3p inhibitory subunit are important determinants of salt tolerance, cell wall integrity and cell cycle progression [1].
  • Therefore, Hal3p might modulate diverse physiological functions of the Ppz1 phosphatase, such as salt stress tolerance and cell cycle progression, by acting as a inhibitory subunit [2].
  • Previous work has shown that yeast cells deficient in Ppz1 protein phosphatase or overexpressing Hal3p, a novel regulatory protein of unknown function, exhibit increased resistance to sodium and lithium, whereas cells lacking Hal3p display increased sensitivity [2].
  • These results are consistent with a model in which the Ppz1-Hal3 interaction is a sensor of intracellular pH that modulates H+ and K+ homeostasis through the regulation of Trk1p activity [3].
  • We show here that the described effects of HAL3/SIS2 on sit4 mutants are fully mediated by the Ppz1 phosphatase [4].

Biological context of SIS2

  • High-copy-number expression of HAL3/SIS2 has been reported to improve cell growth and to increase expression of G1 cyclins in sit4 phosphatase mutants [4].
  • The Saccharomyces cerevisiae SIS2 gene was identified by its ability, when present on a high copy number plasmid, to increase dramatically the growth rate of sit4 mutants [5].
  • These results reveal a role for Ppz1 as a regulatory component of the yeast cell cycle, reinforce the notion that Hal3/Sis2 serves as a negative modulator of the biological functions of Ppz1, and indicate that the Sit4 and Ppz1 Ser/Thr phosphatases play opposite roles in control of the G1/S transition [4].
  • The ability of different genes to suppress sit4 phenotypes (such as temperature sensitivity and growth on non-fermentable carbon sources) or to mimic the functions of Hal3 was evaluated [6].
  • The activity of CtHAL3 was equivalent to that of an open reading frame (YKL088w) identified by genome sequencing of S. cerevisiae and with homology to HAL3 [7].

Regulatory relationships of SIS2


Other interactions of SIS2

  • These results indicate that, besides its role as Ppz1 inhibitory subunit, Vhs3 (and probably Hal3) might have important Ppz-independent functions [9].
  • The salt-tolerance gene HAL3 from Saccharomyces cerevisiae encodes a novel regulatory protein (Hal3p) which modulates the expression of the ENA1 sodium-extrusion ATPase (Ferrando et al., Mol. Cell. Biol. vol. 15, 1995, pp. 5470-5481) [7].
  • We reported that, in the yeast Saccharomyces cerevisiae, overexpression of the Ptc3p isoform resulted in increased lithium tolerance in the hypersensitive hal3 background [10].
  • Deletion of PTC1 in a hal3 background did not exacerbate the halosensitive phenotype of the hal3 strain [10].
  • Taken together, these observations suggest that calcineurin, Hal3, and Lic4 cooperatively regulate the response of yeast cells to cation stress [11].


  1. The Ppz protein phosphatases are key regulators of K+ and pH homeostasis: implications for salt tolerance, cell wall integrity and cell cycle progression. Yenush, L., Mulet, J.M., Ariño, J., Serrano, R. EMBO J. (2002) [Pubmed]
  2. The yeast halotolerance determinant Hal3p is an inhibitory subunit of the Ppz1p Ser/Thr protein phosphatase. de Nadal, E., Clotet, J., Posas, F., Serrano, R., Gomez, N., Ariño, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. pH-Responsive, posttranslational regulation of the Trk1 potassium transporter by the type 1-related Ppz1 phosphatase. Yenush, L., Merchan, S., Holmes, J., Serrano, R. Mol. Cell. Biol. (2005) [Pubmed]
  4. The yeast ser/thr phosphatases sit4 and ppz1 play opposite roles in regulation of the cell cycle. Clotet, J., Garí, E., Aldea, M., Ariño, J. Mol. Cell. Biol. (1999) [Pubmed]
  5. Overexpression of SIS2, which contains an extremely acidic region, increases the expression of SWI4, CLN1 and CLN2 in sit4 mutants. Di Como, C.J., Bose, R., Arndt, K.T. Genetics (1995) [Pubmed]
  6. Identification of multicopy suppressors of cell cycle arrest at the G1-S transition in Saccharomyces cerevisiae. Muñoz, I., Simón, E., Casals, N., Clotet, J., Ariño, J. Yeast (2003) [Pubmed]
  7. CtCdc55p and CtHa13p: two putative regulatory proteins from Candida tropicalis with long acidic domains. Rodriguez, P.L., Ali, R., Serrano, R. Yeast (1996) [Pubmed]
  8. The transcriptional activator Imp2p maintains ion homeostasis in Saccharomyces cerevisiae. Masson, J.Y., Ramotar, D. Genetics (1998) [Pubmed]
  9. Functional characterization of the Saccharomyces cerevisiae VHS3 gene: a regulatory subunit of the Ppz1 protein phosphatase with novel, phosphatase-unrelated functions. Ruiz, A., Muñoz, I., Serrano, R., González, A., Simón, E., Ariño, J. J. Biol. Chem. (2004) [Pubmed]
  10. Role of protein phosphatases 2C on tolerance to lithium toxicity in the yeast Saccharomyces cerevisiae. Ruiz, A., González, A., García-Salcedo, R., Ramos, J., Ariño, J. Mol. Microbiol. (2006) [Pubmed]
  11. Lic4, a nuclear phosphoprotein that cooperates with calcineurin to regulate cation homeostasis in Saccharomyces cerevisiae. Hemenway, C.S., Heitman, J. Mol. Gen. Genet. (1999) [Pubmed]
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